The leukotrienes and their biological activities, especially their roles in various disease states and conditions have been described. For example, see EP 140,684 (May 8, 1985), which is incorporated herein by reference.
several classes of compounds exhibit ability to inhibit the biosynthesis of leukotrienes in mammals, especially humans.
See, for Example, EP 166,591 (Jan. 2, 1986). The compounds of the present invention are distinguished from those of EP 166,591 in the important feature of possessing a heteroatom at position 3 in place of a hydrogen or carbon substituent. The heteroatom introduces unique electronic and chemical properties into the indole nucleus. The compounds of the present invention are further distinguished in that they uniquely inhibit the biosynthesis of leukotrienes, whereas those of EP 166,591 are antagonists of prostaglandins which also possess leukotriene biosynthesis inhibitory properties.
CH-A 454,858 and CH-A 455,777 teach derivatives of indole-2-acetic acid as useful for the treatment of inflammatory diseases. The compounds of these two Swiss patents are distinguished from those of the present invention by the same chemical differences as in EP 166,591, as well as by differences in the scope of their biological activities.
Walton et al., J. Med. Chem., 11, 1252 (1968) teach certain indole-3-acetic acid derivatives assayed for tumor chemotherapy activity. Walton et al. teach compounds with an alkanoic acid in the 3-position, rather than in the 2-position, and they also lack a heteroatom substituent. The single compound of Walton et al. with a 2-alkanoic acid also lacks a 3-hetero substituent. Walton et al. disclose no useful biological activity for their indole 2-alkanoic acid.
JP-238017 teaches 3-substituted 2-phenylindole derivatives as having lipoxygenase and cyclooxygenase inhibiting activity. In addition to the important differences in biological activities, these compounds possess a phenyl group in the 2-position and are lacking the N-benzyl substituent of the compounds of the present invention.